A young Gary Mitchell met James T. Kirk in 2250, and the two became fast friends following Mitchell's admission into Starfleet Academy in the late 2250s. Cadet Mitchell was a student in Lieutenant Kirk's class. He had been warned by upperclassmen, "You either think or sink." Mitchell, in 2265, remembered Kirk as "a stack of books with legs." In an attempt to divert his friend's attentions and make the class easier to get through, Mitchell set Kirk up with a "little blonde lab technician", whom Kirk almost married.

In the mid-23rd century, during a mission to Deneb IV, Gary Mitchell, with his friend James T. Kirk, was tested for his ability at telepathy. Mitchell had a marked ability of sensing telepathic communication used by the inhabitants of that planet. In at least three cases, he was capable of carrying long telepathic communication with selected inhabitants, scoring eighty percent or higher on comprehension. One night, while in telepathic communication with a female inhabitant, Mitchell suffered from after-effects that lasted for a while. Kirk later stated he'd been worried about Mitchell ever since that night. As a pun, Mitchell referred to the female he had been in contact with as a "nova".

Also during his lifetime he visited Kaferia multiple times, and whenever he visited there he always favored Kaferian apples.

In the 2260s, upon receiving his first command, Kirk asked Mitchell to join him aboard that ship. Kirk and Mitchell took part in a mission to planet Dimorus, where they encountered sentient rodent-like creatures that shot poisonousdarts. Mitchell took one of the darts meant for Kirk, saving Kirk's life but nearly dying himself. (TOS: "Where No Man Has Gone Before")

In reporting Mitchell's experiences on Deneb IV, there was a statement which stated that there were notations for the phrase "In at least three cases" on the rear of the report. This portion of the report was never seen.

In a line of dialogue that was written into the script of "Where No Man Has Gone Before" but was not included in the episode's final edit, Mitchell implied a recollection that Kirk nearly washed him out of the Academy.

Mitchell was briefly stunned by direct contact with the strange energies of the barrier, but he recovered quickly. As his recovery continued, however, he began to display a widening array of psionic abilities, including but probably not limited to:

These abilities, or perhaps the energy itself, began to fundamentally alter Mitchell's personality; he became progressively more emotionally distant, cruel, ruthless, and convinced of his own magnificence. Worse, with the passage of time, his abilities continued to grow stronger at a geometric rate. They were accompanied by only two physical manifestations: a curious silver light or glimmer that appeared in Mitchell's eyes, and a later accelerated graying of his hair, beginning at the temples and sideburns.

Damaged by the galactic barrier, the Enterprise limped to Delta Vega. By the time they reached that planet, Kirk was convinced that Mitchell was dangerous, and attempted to maroon him there. They rigged the station to blow up and hopefully kill Mitchell if he tried to break out. But before repairs were complete, Mitchell had grown too strong to be confined. He killed Lee Kelso, left Kirk and Spock stunned, and escaped into the hills around the lithium cracking station, taking another member of the crew, Dr.Elizabeth Dehner, with him.

Recovering, Kirk took a phaser rifle and set out in pursuit. He left orders for Spock; if Kirk had not contacted the ship in twelve hours, Spock was to leave with the Enterprise and recommend Delta Vega be subjected to a lethal concentration of neutron radiation.

Kirk fires a phaser rifle at Mitchell

Mitchell, meanwhile, was using his power to establish a pleasant environment for himself, materializing trees and other objects. Sensing Kirk's approach, he sent Dr. Dehner to meet Kirk, where Kirk discovered that Dehner had undergone the same transformation. It took a little longer for her, perhaps because she didn't have quite as high an esper rating as Mitchell. Kirk attempted to appeal to her remaining Humanity, and when this seemed to be working, a disappointed Mitchell appeared. Mitchell, at least in his own mind, had already transcended mere Humanity.

Dr. Dehner had enough Humanity left to be appalled at Mitchell's actions, and she used her new powers to attack him. At the cost of her own life, she weakened Mitchell long enough for Kirk to overpower him. Kirk knocked Mitchell into a hole Mitchell had prepared (ironically) as Kirk's grave. Using a phaser, Kirk collapsed a hillside on top of Mitchell, burying him beneath tons of rock and ending his threat forever.

In his log, Kirk recorded that Mitchell and Dehner had both died in the line of duty, noting that neither one of them asked for what had happened to them. (TOS: "Where No Man Has Gone Before")

In the revised first draft script of "Where No Man Has Gone Before" (dated 27 May1965), Mitchell's first name was "Clark" and his rank was lieutenant. The same script referred to him, prior to his transformation, thus; "He is about thirty years old, a tall, handsome man with an easy likeable grin, happy-go-lucky look."

Much consideration went into the character of Gary Mitchell and his progression to godly status. For instance, in a four-page memo of notes that director James Goldstone wrote about the second draft script of "Where No Man Has Gone Before", Goldstone raised a point about Mitchell's development that the director described as "major," going on to say, "The purpose is dramatic, to create a subtext... My proposal is that from the time Gary suffers the first realization of what is happening to him... once he begins to give in to it, to enjoy it, even, he moves from his Human status toward the status of a god within all and any of the criteria we place on such deities in our Christian-Judaic culture. Specifically, I propose that he become oracular, in the sense of Moses or even Cotton Mather. I propose he do this in his stature, his way of using his hands and arms and eyes, silver or normal, his attitude as it applies to the script, aside from those specific stage directions, perhaps physical actions, that pertain to the dialogue. I don't mean to suggest that it become so stylized as to become a symbol rather than a Human being. I suggest it happen on a more symbolic level. This can be done by starting him more on the flip, swinging level of articulation so that we don't even notice at one moment that this drops, but it does, on its way to becoming more formal, then more laden with import, more self-declarative, and finally downright miraculous." (The Star Trek Interview Book, pp. 108–109)

By the time the revised final draft of the script for "Where No Man Has Gone Before" (dated 8 July1965) was submitted, Mitchell had the rank of lieutenant commander. Furthermore, the script characterized him, prior to his transformation, as, "about thirty, extremely likeable, and pleasant type [....] He is obviously well known too and liked [....] It's easy to like Mitchell." After being affected by the galactic barrier, he remarked, "I sort of... lean on people I like," in regards to the incident with the "little blonde lab technician" and Kirk, though this line of dialogue was included only in the script and was not present in the episode's final version. Another ultimately unused line of dialogue had Mitchell saying about his empathic ability, while confined to sickbay, "I can catch only flashes so far – mostly strong thoughts, like fear." In yet more dialogue that was scripted but did not make it into the episode, Mitchell promised Elizabeth Dehner, "Soon we will fully control our bodies. We'll never grow old."

A facet of the Gary Mitchell character that was scripted but never made it to screen was a habit of saying "five-oh"; Mitchell used this phrase twice in scripted dialogue that was not in the final edit. Also, Mitchell's relationship with Kirk and Spock was changed to being less focused on Spock.

One script description of Gary Mitchell's mutated look specifies that makeup was to be used to show that "his skin is now shiny smooth, with almost a metallic solidity."

Samuel A. Peeples, the writer of "Where No Man Has Gone Before", believed that an all-powerful man such as Gary Mitchell would not have to resort to violence and, for this reason, Peeples was opposed to the addition of Mitchell's fight scene against Kirk. The reason the scene remained was that Gene Roddenberry was insistent on its inclusion. (The Star Trek Interview Book, p. 119)

The casting of Gary Lockwood as Mitchell was decided on by James Goldstone and Gene Roddenberry. In retrospect, Goldstone recalled how Lockwood was cast in the part; "I had a very good relationship with Gary, as did Gene [Roddenberry], and when we did the pilot Gary was our unanimous choice because we wanted that almost animalistic, very physical person." (The Star Trek Interview Book, p. 105) It was Robert Justman who selected stuntman Hal Needman for the part. (Inside Star Trek: The Real Story, p. 75)

Because Gary Lockwood was extremely busy, Gene Roddenberry at first had to convince him to take the role of Gary Mitchell. The earliest impressions that Lockwood had of the character were colored by a joke that Roddenberry made about "Where No Man Has Gone Before". "He said, 'In it, you'll play a character who becomes sort of God,' and then, he paused and said, 'something, of course, you always thought you were,'" recounted the actor. With a chuckle, he concluded, "I thought that was funny." (Starfleet Access for "Where No Man Has Gone Before", TOS Season 1 Blu-ray special features) Lockwood also remarked, "People always thought I was egotistical, so when I got to play that part, many people laughed and said, 'He has finally found his niche.' That has been a joke among my friends." (Starlog issue #124, p. 44)

In his approach to the character of Gary Mitchell, Gary Lockwood tried (as best he could) to adapt his mindset to that of Mitchell, rather than attempting to make the role fit himself, and endeavored to avoid overemphasizing the character's behavior. He found, however, that playing the part was not easy. "Gary Mitchell was a tough character to reach," Lockwood mused, "because there's no prototype character to look at. So, you create a mental image and try to fill that slot. All I tried to do was downplay the mechanics and not be too dramatic [....] The idea was to go to the character, and not make the character comfortable to me. I'm not Gary Mitchell." (Starlog issue #124, p. 44)

The silver contact lenses worn by Gary Lockwood were extremely primitive. They caused the actor severe pain if left in for more than a few minutes, and when worn, Lockwood could only see through a tiny pinhole opening. Robert Justman later commented, "In order to have any vision at all, Gary had to raise his chin and look down his nose at the other actor in the shot. Happily, this gave him an unearthly appearance that worked well for his character and even helped his godlike progression." (Inside Star Trek: The Real Story, pp. 80–81) Judith Reeves-Stevens also remarked she was sure that Lockwood tilting his head back, due to having to incorporate the presence of the contact lenses in his performance, was "part of him showing an arrogance, in the character." (Starfleet Access for "Where No Man Has Gone Before", TOS Season 1 Blu-ray special features)

Another element of Gary Mitchell's gradual mutation was that his hair became progressively grayer, throughout the episode. Dave Rossi, VFX Line Producer for Remastered TOS, commented that, by giving Mitchell this facet of his appearance, the production staff intended "to use [his abilities] as a drain on his physical body." (Starfleet Access for "Where No Man Has Gone Before", TOS Season 1 Blu-ray special features)

The biographical records Spock researched indicated that Mitchell's birth city, Eldman, was listed in a state, colony or province starting with "New", but his record was cropped and didn't show the complete name, the nation, or even the planet of his birth. It also listed his age as "23" and his height as "5' 9", but Dr. Dehner's record shows two more letters in the state of "Newst..." which could be the same location. It was unknown if the medical record shown was a recent one or from Mitchell's last examination, but it was later stated that he had known Kirk for fifteen years.

Roberto Orci once revealed he had never given serious consideration to using Gary Mitchell as an antagonist in the filmStar Trek Into Darkness. "Just couldn't [get] my mind [around] an ultimate villain named Gary," he professed. "Imagine the trailer: 'In the history of the Galaxy, evil has had many names… Darth Vader… Khan… now, prepare for the greatest foe ever faced by humanity… GARY…" [1]

Nonetheless, Gary Mitchell was one candidate rumored to possibly be an antagonist in Star Trek Into Darkness. Before the movie was released, a name for the villain was revealed to be "John Harrison", though whether this was his actual name or merely an alias was undisclosed. Star Trek Magazine, in the lead-up to the film's release, speculated a 75% probability that the character would turn out to be Mitchell. (Star Trek Magazine issue 172, p. 34)

The back story of how Kirk and Mitchell met was filled in the three-part novel series My Brother's Keeper. It explained how they met, Kirk's emotional turmoil at killing his best friend, as well as explaining technical goofs. The "R" for Kirk's middle name was explained as an in-joke, in which Kirk had said his middle name was "Racquetball." The novel Enterprise gives the names of his parents as Dana and Thomas Mitchell.

In the Q-Zone novels, it was discovered that the Q had set up the galactic barrier to prevent a being called 0 from re-entering the Milky Way Galaxy. Gary Mitchell and Dehner were infected with a "piece" of 0 and that was the origin of their powers.

In Q-Squared, it was revealed that the galactic barrier had trapped the essence of Q after a confrontation with Trelane had scattered him across both time and space. Q failed in an attempt to escape the barrier by attaching himself to an SS Valiant crew member but succeeded, two hundred years later, by attaching himself to Mitchell and Dehner. The same novel also explained the James R. Kirk inconsistency, by placing the events of that episode in a parallel universe ("Track A", as opposed to the normal Star Trek universe's "Track B") where Kirk has a different middle name.

Mitchell would appear as the antagonist in the Star trek/X-men crossover comic where he fuses with Proteus, an X-villian with similar reality warping abilities.

Gary Mitchell in the alternate reality

The Gary Mitchell (β) from the alternate reality created by Nero appeared in the first two issues of the IDW Star Trek series; having been assigned to the Enterprise at Kirk's request, Mitchell again succumbed to the barrier's influence – a Vulcan mind meld performed by Spock confirmed that there was no intelligence in Mitchell after the barrier took over – but during the confrontation on Delta Vega, while Mitchell was tormenting Kirk, he was defeated when Spock sneaked up on the occupied Mitchell and delivered a Vulcan nerve pinch, incapacitating Mitchell long enough for his real self to take over and ask Kirk to kill him. Mitchell was then "killed" by a phaser blast, his body put into a torpedo tube and blasted into space like Spock in Star Trek II: The Wrath of Khan. The Enterprise left Delta Vega's orbit as Mitchell's torpedo tube was left floating in space at the conclusion of this issue. The Elizabeth Dehner (β)/Mitchell pairing does not occur owing to an awkward past relationship with Leonard McCoy that resulted in her cancelling her transfer to USS Enterprise when she found out McCoy was on board.